The biomedical and genetic analysis of natural populations of mammals has been utilized to reveal genomic adaptations relative to oncogenesis, congenital, and infectious diseases. Lessons of historic and ongoing epidemics and ensuing genomic adaptations are critical to interpreting the functional context of genome organization. Population screens of baseline medical genetics and reproductive physiologies offer recurring new insight into biological strategies that influence species survival and provide a fuller understanding of the interaction on species genomes and their biological environment. Using the methods of molecular genetics (allozyme, two dimensional electrophoresis, restriction fragment length polymorphism of nuclear and mitochondrial DNA, and polymerase chain reaction) to monitor sequence variation, several components that influence stability of natural populations have been discovered. Historic inbreeding has been deduced in endangered populations of cheetahs, lions, Florida panthers and black-footed ferrets. The consequences of these inbreeding events included inbreeding depression as reflected in congenital defects and physiological impairment to reproduction. Further, as inbreeding reduces genetic diversity, these events increase suscepti- bility and vulnerability of populations to infectious disease vectors that occasionally evolve mechanisms to abrogate immune differences. Natural examples of the balance of genetic resistance and pathogen evolution revealed a useful model for human infectious diseases.